Soluble CD14 Levels Reflect Liver Inflammation in Patients with Nonalcoholic Steatohepatitis

Ogawa, Yasuhiro; Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Tomeno, Wataru; Shinohara, Yoshiyasu; Kato, Shingo; Mawatari, Hironori; Nozaki, Yuichi; Fujita, Koji; Kohno, Hiroyuki; Maeda, Shin; Saito, Satoru; Wada, Koichiro; Nakajima, Atsushi

doi:10.1371/journal.pone.0065211

Cited by 44 publications

(43 citation statements)

References 37 publications

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“…sCD14 levels increase in response to bacterial infections and endotoxin exposure [24]. iFABP is a marker of intestinal epithelial dysfunction and increases if the epithelial barrier is compromised or injured [25].…”

Section: Resultsmentioning

confidence: 99%

Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD

et al. 2016

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Intestinal dysbiosis and elevated lipopolysaccharides (LPS) levels have been implicated in the development of obesity, insulin resistance and non-alcoholic steatohepatitis (NASH). In order to determine if LPS levels are elevated in patients with NASH compared to patients with non-alcoholic fatty liver (NAFL) and, if elevated LPS levels correlated with histological severity of non-alcoholic fatty liver disease (NAFLD) we compared LPS, markers of LPS bioactivity and pro-inflammatory cytokines/chemokines in patients undergoing bariatric surgery. At the time of surgery a liver biopsy was taken allowing the stratification into well-delineated subgroups including: No NAFL/NAFL; NASH; NASH with fibrosis and NASH cirrhotics, using the NAFLD Activity Score (NAS). Anthropometric data and plasma were collected for assessment of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14), intestinal-type fatty acid binding protein (iFABP), Toll-like receptors 2 and 4 (TLR2, 4) and a panel of cytokines/chemokines. Similar analysis was performed on plasma from a cohort of healthy controls. Our data indicate elevated levels of LPS, LBP, sCD14, iFABP and TLR2,4 in obese patients compared to healthy controls, however, these parameters remained unaltered within patients with limited liver disease (NAFL) compared to NASH/NASH with fibrosis subgroups. Hierarchic cluster analysis using endotoxin-related parameters failed to discriminate between lean controls, NAFLD. While similar cluster analysis implementing inflammation-related parameters clearly distinguished lean controls, NALFD subgroups and NASH cirrhotics. In addition, LPS levels was not associated with disease severity while TNFα, IL8, and CCL3 featured a clear correlation with transaminase levels and the histological severity of NALFD. In conclusion our data indicate a stronger correlation for circulating inflammatory- rather than endotoxin-related parameters in progression of NAFLD and highlights the need for additional larger studies in unravelling further mechanistic insights.

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Section: Resultsmentioning

confidence: 99%

Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD

et al. 2016

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“…Persistent inflammation promotes hepatic triglyceride accumulation and NASH. toxins in the progression of NAFLD (66)(67)(68)(69)(70)(71)(72)(73). Studies related to endotoxemia and NAFLD progression are summarized in Tables 3 and 4.…”

Section: Hfd Fed Andmentioning

confidence: 99%

Role of gut microbiota: Obesity and NAFLD

Gangarapu¹,

Yıldız²,

İnce³

et al. 2014

Turk J Gastroenterol

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Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease in developed countries. Obesity is the most important risk factor for metabolic syndrome and NAFLD. Accumulated evidence has revealed that gut microbial compositional changes may be associated with more energy harvesting from the diet, which promotes increased fatty acid uptake from adipose tissue and shifts lipid metabolism from oxidation to de novo production. Furthermore, changes in intestinal barrier function contribute to metabolic endotoxemia in the form of low-grade microbial inflammation. Persistent inflammation exacerbates NAFLD progression. In this review, we discuss the role of gut microbiota in obesity and NAFLD.

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“…French et al [65] provided evidence that in HIV/hepatitis C virus (HCV)-coinfection, levels of sCD14 and IL-6 were mostly elevated in patient with disease progression than in non-progressors. Studies in patients with NAFLD reached similar results, suggesting a positive correlation between serum sCD14, hepatic CD14 expression and liver inflammation [66] . Attention has also been drawn towards polymorphisms of the promoter region of the CD14 gene, shedding light to the role of CD14/-159TT genotype in the progression of liver injury in alcoholic liver disease [67] .…”

Section: Lps-lbp-scd14mentioning

confidence: 53%

“…Landmann et al [61] , Tuomisto et al [62] , Sandler et al [63] , Balagopal et al [64] , French et al [65] , Ogawa et al [66] , Campos et al [67] Calprotectin Neutrophils Pros: Easily measured, fecal levels associated with stage of liver disease, SBP and HE, ratio of ascites calprotectin/total protein may be better…”

Section: Bacterial Dnamentioning

confidence: 99%

Markers of bacterial translocation in end-stage liver disease

Koutsounas¹,

Kaltsa²,

Siakavellas³

et al. 2015

WJH

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Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence.BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.

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Soluble CD14 Levels Reflect Liver Inflammation in Patients with Nonalcoholic Steatohepatitis

Cited by 44 publications

References 37 publications

Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD

Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD

Role of gut microbiota: Obesity and NAFLD

Markers of bacterial translocation in end-stage liver disease

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